Denda Mitsuhiro, Fuziwara Shigeyoshi, Inoue Kaori
Shiseido Research Center, Yokohama, Japan.
J Invest Dermatol. 2004 Jan;122(1):140-6. doi: 10.1046/j.0022-202X.2003.22115.x.
Activation of Gs protein increases the intracellular cyclic adenosine monophosphate (cAMP) level, and the Gs protein-linked receptor has been implicated in the skin barrier homeostasis. In this study, we investigated the role of cAMP in epidermal barrier function. The barrier was disrupted by tape stripping or treatment with acetone. Immediately after barrier disruption, reagents affecting the cAMP level were topically applied. Topical application of forskolin, which activates cAMP synthesis delayed barrier recovery, whereas application of the antagonist of cAMP, cAMP-Rp, accelerated barrier recovery. Moreover, application of 9-cyclopentyladenine, an inhibitor of cAMP synthesis also accelerated barrier recovery. Tape stripping was found to increase the cAMP in the epidermis. Light and electron microscopic observations showed the delay of lamellar body secretion by forskolin and acceleration of the lamellar body secretion by cAMP-Rp. Application of an inhibitor of protein kinase A did not affect the barrier recovery rate. The delay of barrier recovery induced by forskolin was blocked by the voltage-gated calcium channel blockers, nifedipine and verapamil. In cultured keratinocytes, forskolin increased the intracellular calcium concentration and both nifedipine and verapamil blocked the increase. These results suggest that intracellular cAMP in the epidermis is involved in skin barrier homeostasis.
Gs蛋白的激活会增加细胞内环磷酸腺苷（cAMP）水平，且Gs蛋白偶联受体与皮肤屏障稳态有关。在本研究中，我们调查了cAMP在表皮屏障功能中的作用。通过胶带剥离或丙酮处理破坏屏障。屏障破坏后立即局部应用影响cAMP水平的试剂。激活cAMP合成的福斯高林局部应用会延迟屏障恢复，而cAMP拮抗剂cAMP-Rp的应用则加速屏障恢复。此外，cAMP合成抑制剂9-环戊基腺嘌呤的应用也加速了屏障恢复。发现胶带剥离会增加表皮中的cAMP。光镜和电镜观察显示，福斯高林会延迟板层小体分泌，而cAMP-Rp会加速板层小体分泌。应用蛋白激酶A抑制剂不影响屏障恢复率。福斯高林诱导的屏障恢复延迟被电压门控钙通道阻滞剂硝苯地平和维拉帕米阻断。在培养的角质形成细胞中，福斯高林增加细胞内钙浓度，硝苯地平和维拉帕米均能阻断这种增加。这些结果表明，表皮中的细胞内cAMP参与皮肤屏障稳态。
